transcription factor relb


Summary: A transcription factor that takes part in the NF-kappa-B complex by interacting with NF-KAPPA B P50 SUBUNIT or NF-KAPPA B P52 SUBUNIT. It regulates GENETIC TRANSCRIPTION that is involved in immune and inflammatory responses.

Top Publications

  1. O Sullivan B, Pai S, Street S, An X, MacDonald K, Wong M, et al. Immunotherapy with costimulatory dendritic cells to control autoimmune inflammation. J Immunol. 2011;187:4018-30 pubmed publisher
    ..IFN-? and IDO activity may be good surrogate biomarkers measured against clinical efficacy in trials of autoimmune disease immunoregulation. ..
  2. Chen X, Yoza B, El Gazzar M, Hu J, Cousart S, McCall C. RelB sustains IkappaBalpha expression during endotoxin tolerance. Clin Vaccine Immunol. 2009;16:104-10 pubmed publisher
    ..We conclude that RelB functions as a dual transcription regulator during LPS tolerance and human SSI by activating and repressing innate immunity genes. ..
  3. Maier H, Marienfeld R, Wirth T, Baumann B. Critical role of RelB serine 368 for dimerization and p100 stabilization. J Biol Chem. 2003;278:39242-50 pubmed
    ..Wild type RelB, but not mutant RelB, prolonged p100 half-life. We therefore suggest an inhibitory effect of RelB on p100 processing, which is possibly regulated in a signal-dependent manner. ..
  4. Thompson A, Pettit A, Padmanabha J, Mansfield H, Frazer I, Strutton G, et al. Nuclear RelB+ cells are found in normal lymphoid organs and in peripheral tissue in the context of inflammation, but not under normal resting conditions. Immunol Cell Biol. 2002;80:164-9 pubmed
    ..Nuclear RelB+ cells are found in normal lymphoid organs and in peripheral tissue in the context of inflammation, but not under normal resting conditions. ..
  5. Solan N, Miyoshi H, Carmona E, Bren G, Paya C. RelB cellular regulation and transcriptional activity are regulated by p100. J Biol Chem. 2002;277:1405-18 pubmed
    ..Thus, these studies indicate that p100 is a bone fide inhibitor of RelB and that this transcription factor may be regulated by NF-kappaB-inducing kinase and/or IKKalpha. ..
  6. Kobayashi T, Walsh P, Walsh M, Speirs K, Chiffoleau E, King C, et al. TRAF6 is a critical factor for dendritic cell maturation and development. Immunity. 2003;19:353-63 pubmed
    ..Together these results indicate that TRAF6 regulates the critical processes required for maturation, activation, and development of DCs, the primary cellular bridge between innate and adaptive immunity. ..
  7. Hailfinger S, Nogai H, Pelzer C, Jaworski M, Cabalzar K, Charton J, et al. Malt1-dependent RelB cleavage promotes canonical NF-kappaB activation in lymphocytes and lymphoma cell lines. Proc Natl Acad Sci U S A. 2011;108:14596-601 pubmed publisher
    ..These findings identify a central role for Malt1-dependent RelB cleavage in canonical NF-?B activation and thereby provide a rationale for the targeting of Malt1 in immunomodulation and cancer treatment. ..
  8. Sasaki C, Ghosh P, Longo D. Recruitment of RelB to the Csf2 promoter enhances RelA-mediated transcription of granulocyte-macrophage colony-stimulating factor. J Biol Chem. 2011;286:1093-102 pubmed publisher
    ..Moreover, the novel priming process described here underscores the complexity of the interactions between the classical and alternative NF-?B signaling pathways. ..
  9. Dimitrakopoulos F, Antonacopoulou A, Kottorou A, Vlotinou H, Panagopoulos N, Dougenis D, et al. NSCLC and the alternative pathway of NF-?B: uncovering an unknown relation. Virchows Arch. 2012;460:515-23 pubmed publisher
    ..Moreover, lymph node metastasis was related to nuclear NF-?B2 expression in tumor cells. The deregulation of the alternative NF-?B pathway in NSCLC could play a role in the development and progression of the disease. ..

More Information


  1. Gasparini C, Foxwell B, Feldmann M. RelB/p50 regulates CCL19 production, but fails to promote human DC maturation. Eur J Immunol. 2009;39:2215-23 pubmed publisher
    ..In conclusion, we demonstrated that RelB/p50 was active only in DC expressing both RelB and p50, and induced CCL19 production, but not DC maturation. ..
  2. El Gazzar M, Yoza B, Hu J, Cousart S, McCall C. Epigenetic silencing of tumor necrosis factor alpha during endotoxin tolerance. J Biol Chem. 2007;282:26857-64 pubmed
    ..These results support an immunodeficiency paradigm where epigenetic changes at the promoter of acute proinflammatory genes mediate their repression during the late phase of severe systemic inflammation. ..
  3. Le Bon A, Montoya M, Edwards M, Thompson C, Burke S, Ashton M, et al. A role for the transcription factor RelB in IFN-alpha production and in IFN-alpha-stimulated cross-priming. Eur J Immunol. 2006;36:2085-93 pubmed
    ..and wild-type (+/+) mice were used to determine how total or partial absence of the transcription factor RelB in haematopoietic cells affects the immune response generated after lymphocytic choriomeningitis virus (..
  4. Lessard L, Begin L, Gleave M, Mes Masson A, Saad F. Nuclear localisation of nuclear factor-kappaB transcription factors in prostate cancer: an immunohistochemical study. Br J Cancer. 2005;93:1019-23 pubmed
    ..018). The nuclear localisation of both canonical and noncanonical NF-kappaB subunits in prostate cancer cells suggests for the first time that different NF-kappaB pathways and dimers may be activated in the progression of the disease. ..
  5. Goldmit M, Ji Y, Skok J, Roldan E, Jung S, Cedar H, et al. Epigenetic ontogeny of the Igk locus during B cell development. Nat Immunol. 2005;6:198-203 pubmed
    ..These results suggest that early B lymphoid epigenetic changes generate differential structures that serve as the basis for allelic exclusion. ..
  6. Saitoh T, Nakano H, Yamamoto N, Yamaoka S. Lymphotoxin-beta receptor mediates NEMO-independent NF-kappaB activation. FEBS Lett. 2002;532:45-51 pubmed
    ..In the absence of NEMO, the p50 and RelB, but not RelA subunits of NF-kappaB are found in the nuclear DNA binding complexes induced by the LTbetaR signaling. Our results thus disclose NEMO-independent NF-kappaB activation by LTbetaR. ..
  7. Shih V, Davis Turak J, Macal M, Huang J, Ponomarenko J, Kearns J, et al. Control of RelB during dendritic cell activation integrates canonical and noncanonical NF-?B pathways. Nat Immunol. 2012;13:1162-70 pubmed publisher
    ..This work illustrates the potential utility of systems analyses in guiding the development of combination therapeutics for modulating DC-dependent T cell responses. ..
  8. Baeuerle P, Baltimore D. NF-kappa B: ten years after. Cell. 1996;87:13-20 pubmed
  9. Ishimaru N, Kishimoto H, Hayashi Y, Sprent J. Regulation of naive T cell function by the NF-kappaB2 pathway. Nat Immunol. 2006;7:763-72 pubmed
    ..Biochemical studies indicated involvement of a cell-intrinsic mechanism in which NF-kappaB2 (p100) limits nuclear translocation of NF-kappaB1-RelA and thereby functions as a regulatory 'brake' for the activation of naive T cells. ..
  10. Powolny Budnicka I, Riemann M, Tänzer S, Schmid R, Hehlgans T, Weih F. RelA and RelB transcription factors in distinct thymocyte populations control lymphotoxin-dependent interleukin-17 production in ?? T cells. Immunity. 2011;34:364-74 pubmed publisher
    ..Thus, RelA and RelB within different thymocyte subpopulations cooperate in the regulation of IL-17 production by ?? T cells and contribute to the host's ability to fight bacterial infections. ..
  11. Weih F, Carrasco D, Durham S, Barton D, Rizzo C, Ryseck R, et al. Multiorgan inflammation and hematopoietic abnormalities in mice with a targeted disruption of RelB, a member of the NF-kappa B/Rel family. Cell. 1995;80:331-40 pubmed
    ..Thus, RelB plays a decisive role in the hematopoietic system, and its absence cannot be functionally compensated by any other member of the NF-kappa B/Rel family. ..
  12. Fusco A, Huang D, Miller D, Wang V, Vu D, Ghosh G. NF-kappaB p52:RelB heterodimer recognizes two classes of kappaB sites with two distinct modes. EMBO Rep. 2009;10:152-9 pubmed publisher
    ..We suggest that the p52:RelB heterodimer is more adaptable to complement sequence and structural variations in kappaB sites when compared with other NF-kappaB dimers. ..
  13. Basak S, Shih V, Hoffmann A. Generation and activation of multiple dimeric transcription factors within the NF-kappaB signaling system. Mol Cell Biol. 2008;28:3139-50 pubmed publisher
    ..Our results inform a wiring diagram to delineate NF-kappaB dimer formation that emphasizes that inflammatory and developmental signaling cannot be considered separately but are highly interconnected. ..
  14. Jacque E, Tchenio T, Piton G, Romeo P, Baud V. RelA repression of RelB activity induces selective gene activation downstream of TNF receptors. Proc Natl Acad Sci U S A. 2005;102:14635-40 pubmed
  15. Weih F, Durham S, Barton D, Sha W, Baltimore D, Bravo R. p50-NF-kappaB complexes partially compensate for the absence of RelB: severely increased pathology in p50(-/-)relB(-/-) double-knockout mice. J Exp Med. 1997;185:1359-70 pubmed
    ..These results indicate that the lack of RelB is, in part, compensated by other p50-containing complexes and that the "classical" p50-RelA-NF-kappaB activity is not required for the development of the inflammatory phenotype. ..
  16. Yilmaz Z, Weih D, Sivakumar V, Weih F. RelB is required for Peyer's patch development: differential regulation of p52-RelB by lymphotoxin and TNF. EMBO J. 2003;22:121-30 pubmed
    ..Our data indicate an important role of p52-RelB heterodimers in lymphoid organ development downstream of LTbetaR, NIK and IKKalpha. ..
  17. Barton D, HogenEsch H, Weih F. Mice lacking the transcription factor RelB develop T cell-dependent skin lesions similar to human atopic dermatitis. Eur J Immunol. 2000;30:2323-32 pubmed
    ..Thus, the relB(- / -) mouse should be a useful model to study the pathogenesis of this common allergic human disease. ..
  18. Weih D, Yilmaz Z, Weih F. Essential role of RelB in germinal center and marginal zone formation and proper expression of homing chemokines. J Immunol. 2001;167:1909-19 pubmed
    ..Our data indicate that activation of p52-RelB heterodimers in stromal cells downstream of TNF/lymphotoxin is required for normal expression of homing chemokines and proper development of spleen microarchitecture. ..
  19. Lwin T, Hazlehurst L, Li Z, Dessureault S, Sotomayor E, Moscinski L, et al. Bone marrow stromal cells prevent apoptosis of lymphoma cells by upregulation of anti-apoptotic proteins associated with activation of NF-kappaB (RelB/p52) in non-Hodgkin's lymphoma cells. Leukemia. 2007;21:1521-31 pubmed
    ..Consequently, this study suggests a new approach to decrease the resistance of lymphoma to chemotherapy. ..
  20. Landowski T, Olashaw N, Agrawal D, Dalton W. Cell adhesion-mediated drug resistance (CAM-DR) is associated with activation of NF-kappa B (RelB/p50) in myeloma cells. Oncogene. 2003;22:2417-21 pubmed
    ..These data demonstrate the selectivity of signal transduction from the microenvironment that may contribute to tumor cell resistance to programmed cell death. ..
  21. Zanetti M, Castiglioni P, Schoenberger S, Gerloni M. The role of relB in regulating the adaptive immune response. Ann N Y Acad Sci. 2003;987:249-57 pubmed
    ..It is found that the DCs in these mice are profoundly deficient in their ability to both prime and cross-prime T cell responses. It was concluded that the relB gene is involved in regulating the APC function of DCs in vivo. ..
  22. Yoza B, Hu J, Cousart S, Forrest L, McCall C. Induction of RelB participates in endotoxin tolerance. J Immunol. 2006;177:4080-5 pubmed
    ..Taken together, our findings demonstrate that RelB can repress proinflammatory gene expression, and suggest that RelB expression in sepsis patient blood leukocytes may play a role in the endotoxin-tolerant phenotype. ..
  23. Weih F, Durham S, Barton D, Sha W, Baltimore D, Bravo R. Both multiorgan inflammation and myeloid hyperplasia in RelB-deficient mice are T cell dependent. J Immunol. 1996;157:3974-9 pubmed
    ..Thus, both multiorgan inflammation and myeloid hyperplasia in RelB-deficient mice are T cell dependent, whereas B cells are not crucially involved. ..
  24. Neumann M, Wohlleben G, Chuvpilo S, Kistler B, Wirth T, Serfling E, et al. CD40, but not lipopolysaccharide and anti-IgM stimulation of primary B lymphocytes, leads to a persistent nuclear accumulation of RelB. J Immunol. 1996;157:4862-9 pubmed
    ..Since LPS and anti-IgM were unable to activate RelB, CD40 appears to trigger a special program of gene expression involved in the proliferation and/or differentiation of B lymphocytes. ..
  25. Carrasco D, Ryseck R, Bravo R. Expression of relB transcripts during lymphoid organ development: specific expression in dendritic antigen-presenting cells. Development. 1993;118:1221-31 pubmed
    ..Our observations indicate that RelB may play a particular role in the signal transduction pathway that regulate dendritic cell differentiation and its cellular responses. ..
  26. Wu L, D Amico A, Winkel K, Suter M, Lo D, Shortman K. RelB is essential for the development of myeloid-related CD8alpha- dendritic cells but not of lymphoid-related CD8alpha+ dendritic cells. Immunity. 1998;9:839-47 pubmed
    The transcription factor RelB had been shown to be important for dendritic cell (DC) development, but the type of DC involved was not clear...
  27. Ghosh S, May M, Kopp E. NF-kappa B and Rel proteins: evolutionarily conserved mediators of immune responses. Annu Rev Immunol. 1998;16:225-60 pubmed
    ..In this review, we discuss some of these recent findings and their implications for the study of NF-kappa B. ..
  28. Xu Y, Josson S, Fang F, Oberley T, St Clair D, Wan X, et al. RelB enhances prostate cancer growth: implications for the role of the nuclear factor-kappaB alternative pathway in tumorigenicity. Cancer Res. 2009;69:3267-71 pubmed publisher
  29. Gerondakis S, Grossmann M, Nakamura Y, Pohl T, Grumont R. Genetic approaches in mice to understand Rel/NF-kappaB and IkappaB function: transgenics and knockouts. Oncogene. 1999;18:6888-95 pubmed
    ..Future studies will no doubt focus on the effect of multiple gene disruptions of members of this signaling pathway, on tissue-specific disruptions of these genes, and on the use of these mice as models for human diseases. ..
  30. Heino M, Peterson P, Sillanpää N, Guerin S, Wu L, Anderson G, et al. RNA and protein expression of the murine autoimmune regulator gene (Aire) in normal, RelB-deficient and in NOD mouse. Eur J Immunol. 2000;30:1884-93 pubmed
    ..These results suggest that the Aire protein is associated with the normal development and/or action of a subset of thymic medullary stromal cells involved in tolerance induction. ..
  31. Madge L, May M. The NF?B paradox: RelB induces and inhibits gene expression. Cell Cycle. 2011;10:6-7 pubmed
  32. Beg A, Sha W, Bronson R, Ghosh S, Baltimore D. Embryonic lethality and liver degeneration in mice lacking the RelA component of NF-kappa B. Nature. 1995;376:167-70 pubmed
    ..These results indicate that RelA controls inducible, but not basal, transcription in NF-kappa B-regulated pathways. ..
  33. Castiglioni P, Lu C, Lo D, Croft M, Langlade Demoyen P, Zanetti M, et al. CD4 T cell priming in dendritic cell-deficient mice. Int Immunol. 2003;15:127-36 pubmed
    ..These data demonstrate that CD4( +) T cells can be primed in the absence of functional DC and suggest that relB may gauge the T cell response in vivo. ..
  34. Gray D, Seach N, Ueno T, Milton M, Liston A, Lew A, et al. Developmental kinetics, turnover, and stimulatory capacity of thymic epithelial cells. Blood. 2006;108:3777-85 pubmed
    ..Overall, these studies show that the thymic stroma is a surprisingly dynamic population and may have a more direct role in negative selection than previously thought. ..
  35. Weih F, Warr G, Yang H, Bravo R. Multifocal defects in immune responses in RelB-deficient mice. J Immunol. 1997;158:5211-8 pubmed
    ..Thus, RelB is not only essential for a normal hemopoietic system in the unchallenged animal, but also involved in various specific and nonspecific immune responses. ..
  36. Kahn Perles B, Lipcey C, Lecine P, Olive D, Imbert J. Temporal and subunit-specific modulations of the Rel/NF-kappaB transcription factors through CD28 costimulation. J Biol Chem. 1997;272:21774-83 pubmed
    ..Furthermore, contrary to p65, c-Rel appears to display little affinity for p105, p100 and IkappaBalpha regulators. ..
  37. Choudhary S, Boldogh S, Garofalo R, Jamaluddin M, Brasier A. Respiratory syncytial virus influences NF-kappaB-dependent gene expression through a novel pathway involving MAP3K14/NIK expression and nuclear complex formation with NF-kappaB2. J Virol. 2005;79:8948-59 pubmed
    ..This appears to be through a novel mechanism involving induction of NIK kinase activity, expression, and nuclear translocation of a ternary complex with IKKalpha and processed NF-kappaB2. ..
  38. DeKoning J, DiMolfetto L, Reilly C, Wei Q, Havran W, Lo D. Thymic cortical epithelium is sufficient for the development of mature T cells in relB-deficient mice. J Immunol. 1997;158:2558-66 pubmed
  39. Demicco E, Kavanagh K, Romieu Mourez R, Wang X, Shin S, Landesman Bollag E, et al. RelB/p52 NF-kappaB complexes rescue an early delay in mammary gland development in transgenic mice with targeted superrepressor IkappaB-alpha expression and promote carcinogenesis of the mammary gland. Mol Cell Biol. 2005;25:10136-47 pubmed
    ..Inhibition of RelB in breast cancer cells repressed cyclin D1 and c-Myc levels and growth in soft agar. These results implicate RelB/p52 complexes in mammary gland development and carcinogenesis. ..
  40. Li M, Zhang X, Zheng X, Lian D, Zhang Z, Ge W, et al. Immune modulation and tolerance induction by RelB-silenced dendritic cells through RNA interference. J Immunol. 2007;178:5480-7 pubmed
    ..This study demonstrates for the first time that transplant tolerance can be induced by means of RNA interference using in vitro-generated tolerogenic DC. ..
  41. Lovas A, Radke D, Albrecht D, Yilmaz Z, Möller U, Habenicht A, et al. Differential RelA- and RelB-dependent gene transcription in LTbetaR-stimulated mouse embryonic fibroblasts. BMC Genomics. 2008;9:606 pubmed publisher
    ..Microarray analysis of LTbetaR-stimulated fibroblasts provided comprehensive insight into the transcriptional response of LTbetaR signaling and its regulation by the NF-kappaB family members RelA and RelB. ..
  42. Kistler B, Rolink A, Marienfeld R, Neumann M, Wirth T. Induction of nuclear factor-kappa B during primary B cell differentiation. J Immunol. 1998;160:2308-17 pubmed
    ..Consistent with these observations, I kappa B beta cotransfection can inhibit p50/RelA-mediated trans-activation, but barely affects p50/RelB mediated trans-activation. ..
  43. Harhaj E, Blaney J, Millhouse S, Sun S. Differential effects of I kappa B molecules on Tat-mediated transactivation of HIV-1 LTR. Virology. 1996;216:284-7 pubmed
  44. Chen X, El Gazzar M, Yoza B, McCall C. The NF-kappaB factor RelB and histone H3 lysine methyltransferase G9a directly interact to generate epigenetic silencing in endotoxin tolerance. J Biol Chem. 2009;284:27857-65 pubmed publisher
    ..We previously reported that de novo induction of the NF-kappaB transcription factor RelB by endotoxin activation is necessary and sufficient for silencing transcription of acute proinflammatory ..
  45. Rauert H, Wicovsky A, Muller N, Siegmund D, Spindler V, Waschke J, et al. Membrane tumor necrosis factor (TNF) induces p100 processing via TNF receptor-2 (TNFR2). J Biol Chem. 2010;285:7394-404 pubmed publisher
    ..Thus, we identified activation of the alternative NFkappaB pathway as a TNF signaling effect that can be specifically assigned to TNFR2 and membrane TNF. ..
  46. Madge L, May M. Classical NF-kappaB activation negatively regulates noncanonical NF-kappaB-dependent CXCL12 expression. J Biol Chem. 2010;285:38069-77 pubmed publisher
    ..Our findings therefore demonstrate that TNF-induced classical NF-?B signaling up-regulates RelB expression that inhibits both basal and NC NF-?B-dependent CXCL12 expression. ..
  47. Ruben S, Klement J, Coleman T, Maher M, Chen C, Rosen C. I-Rel: a novel rel-related protein that inhibits NF-kappa B transcriptional activity. Genes Dev. 1992;6:745-60 pubmed
    ..Our findings suggest that p50 and I-Rel are components of a feedback pathway where expression of I-Rel may modulate indirectly the expression of genes responsive to the NF-kappa B transcription factor complex. ..
  48. Liu T, Yoza B, El Gazzar M, Vachharajani V, McCall C. NAD+-dependent SIRT1 deacetylase participates in epigenetic reprogramming during endotoxin tolerance. J Biol Chem. 2011;286:9856-64 pubmed publisher
    ..We conclude that TLR4 stimulation and human sepsis activate pathways that couple NAD(+) and its sensor SIRT1 with epigenetic reprogramming. ..
  49. Rayet B, Gelinas C. Aberrant rel/nfkb genes and activity in human cancer. Oncogene. 1999;18:6938-47 pubmed
    ..This review focuses on the status of the rel, nfkb and ikb genes and their activity in human tumors and their association with the onset or progression of malignancies. ..
  50. Marienfeld R, May M, Berberich I, Serfling E, Ghosh S, Neumann M. RelB forms transcriptionally inactive complexes with RelA/p65. J Biol Chem. 2003;278:19852-60 pubmed
    ..Taken together, our findings demonstrate that sequestration of RelA in transcriptionally inactive RelA.RelB complexes provides a molecular mechanism that may explain the repressive role of RelB on NF-kappaB-dependent gene expression. ..
  51. Bonizzi G, Bebien M, Otero D, Johnson Vroom K, Cao Y, Vu D, et al. Activation of IKKalpha target genes depends on recognition of specific kappaB binding sites by RelB:p52 dimers. EMBO J. 2004;23:4202-10 pubmed
    ..This site links induction of organogenic chemokines and other important regulatory molecules to activation of the alternative pathway. ..
  52. Yang H, Zhang Y, Wu M, Li J, Zhou W, Li G, et al. Suppression of ongoing experimental autoimmune myasthenia gravis by transfer of RelB-silenced bone marrow dentritic cells is associated with a change from a T helper Th17/Th1 to a Th2 and FoxP3+ regulatory T-cell profile. Inflamm Res. 2010;59:197-205 pubmed publisher
  53. Verma I, Stevenson J, Schwarz E, Van Antwerp D, Miyamoto S. Rel/NF-kappa B/I kappa B family: intimate tales of association and dissociation. Genes Dev. 1995;9:2723-35 pubmed